Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1694-7. doi: 10.1016/j.bmcl.2009.01.094. Epub 2009 Jan 31.

Abstract

A series of thiophene PLK1 inhibitors was optimized for increased solubility and reduced protein binding through the appendage of basic amine functionality. Interesting selectivity between PLK1 and PLK3 was also obtained through these modifications.

MeSH terms

  • Cell Cycle
  • Cell Cycle Proteins / antagonists & inhibitors*
  • Cell Cycle Proteins / chemistry
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Mitosis
  • Models, Chemical
  • Molecular Conformation
  • Protein Binding
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / chemistry
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / chemistry
  • Solubility
  • Thiophenes / chemistry*
  • Tumor Suppressor Proteins

Substances

  • Cell Cycle Proteins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Thiophenes
  • Tumor Suppressor Proteins
  • PLK3 protein, human
  • Protein Serine-Threonine Kinases
  • polo-like kinase 1